DESCRIPTION (Taken from the application): Despite impressive advances in understanding of osteoporosis, the cure of osteoporosis remains an elusive goal. When patients present with fractures, the loss of bone has already been quite substantial. An important goal must be to increase the strength of such bone to normal. Since currently available treatments all focus on inhibiting resorption of bone, these treatments cannot restore bone mass to normal. A safe and effective agent that increases bone formation in osteoporotic patients, therefore, is required for the cure of osteoporosis. Parathyroid hormone (PTH), administered by once daily injection to humans or to a variety of animal species, increases bone mass and bone strength by increasing bone formation, and prevents fractures. Consideration of the complicated actions of parathyroid hormone on bone leads to the realization that very little is understood about the basic mechanisms of PTH action. Greater understanding of these basic mechanisms will facilitate the design of strategies for clinical use of PTH. The goal of this proposed SCOR (a continuation of funding begun in October 1997) is to learn how to use parathyroid hormone to treat patients with osteoporosis in the most effective manner. Achievement of this goal will require a combined approach that both evaluates the effects parathyroid hormone in humans and studies the basic mechanisms of parathyroid hormone action in animal models. The SCOR has as its centerpiece a patient-based project that explores the effects of administering PTH to osteoporotic men and women. The goals are to understand the mechanisms of the anabolic action of PTH and, thereby, to determine how best to use PTH in the treatment of osteoporosis. Three projects then explore the cellular and molecular basis of the actions of parathyroid hormone on bone. Each of these three projects studies the actions of PTH on bone in vivo and uses precise genetic manipulations in mice to probe mechanisms without abandoning the complexity of the intact animal. A Bone Analysis Core Facility will provide skills efficiencies in the analysis of samples of blood, urine, and bone that will aid each of the four scientific projects. An Administrative Core will assure that communication between the various projects is optimal and will monitor the progress of each project.